In vitro hematotoxicity of Aplidine on human bone marrow and cord blood progenitor cells

Aplidine is a cyclic depsipeptide that was isolated from a Mediterranean ma rine tunicate, Aplidium albicans. In experimental animals, Aplidine mediate d an in vivo inhibitory effect in a number of tumor cell types. In humans, Aplidine is currently used in phase I clinical trials. Aiming to predict th e hematotoxicity of Aplidine in humans, samples from human bone marrow (BM) and cord blood (CB) were exposed in vitro to increasing concentrations of the drug and then assayed for the clonogenic ability of myeloid (CFU-GM), e rythroid (BFU-E), megakaryocitic (CFU-Meg) and pluripotent (CFU-Mix) hemato poietic progenitors. We investigated whether predictions of the hematotoxic ity of Aplidine based on bone marrow (BM) cultures were reproduced when a m ore readily available source of human hematopoietic cells, cord blood cells , was used in experiments involving 24-h exposures. Although hematopoietic progenitors derived from bone marrow were generally more sensitive than tho se derived from cord blood, differences on the IC50, IC70 and IC90 varied w ithin a relatively small range of 1.6-6.2-fold. Moreover, data obtained fro m cord blood cultures confirmed the observation made in bone marrow assays indicating that the myeloid (CFU-GM) and the erythroid (BFU-E) progenitors were the least sensitive to Aplidine. Regardless of the origin of the hemat opoietic progenitors (bone marrow or cord blood) the toxicity of Aplidine i n human hematopoietic progenitors (IC50: 150-2250 nM) was lower than that o bserved in previous studies with tumoral cell lines. (C) 2001 Elsevier Scie nce Ltd. All rights reserved.